Germain Ronald N
Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Med. 2004 Dec;10(12):1307-20. doi: 10.1038/nm1159.
"Nature has provided, in the white corpuscles as you call them-in the phagocytes as we call them-a natural means of devouring and destroying all disease germs. There is at bottom only one genuinely scientific treatment for all diseases, and that is to stimulate the phagocytes." So opined B.B. in G.B. Shaw's The Doctor's Dilemma in a dramatic restatement of a key portion of Ilya Metchnikoff's Nobel Prize address: "Whenever the organism enjoys immunity, the introduction of infectious microbes is followed by the accumulation of mobile cells, of white corpuscles of the blood in particular which absorb the microbes and destroy them. The white corpuscles and the other cells capable of doing this have been designated 'phagocytes,' (i.e., devouring cells) and the whole function that ensures immunity has been given the name of 'phagocytosis'". Based on these insights into the foundation of resistance to infectious disease, Metchnikoff was awarded the 1908 Nobel Prize in Physiology or Medicine together with Paul Ehrlich (Fig. 1). Although both were cited for discoveries in immunity, the contributions of the two men seem worlds apart. Ehrlich's studies did not deal with generic responses to infection, but rather with the highly specific nature of antibodies and their relationship to the cells producing them: "As the cell receptor is obviously preformed, and the artificially produced antitoxin only the consequence, i.e. secondary, one can hardly fail to assume that the antitoxin is nothing else but discharged components of the cell, namely receptors discharged in excess". But biological systems are just that-systems-and the parts need to work together. And so we arrive, a century later, at an appreciation for just how intimately related these two seemingly disparate aspects of host defense really are.
“大自然赋予了你们所说的白细胞——我们所说的吞噬细胞——一种吞噬和消灭所有病菌的天然手段。归根结底，对所有疾病只有一种真正科学的治疗方法，那就是刺激吞噬细胞。”萧伯纳在《医生的困境》中借B.B.之口戏剧性地重述了伊利亚·梅契尼科夫诺贝尔奖演讲的关键部分：“每当机体具有免疫力时，引入传染性微生物后，就会有游走细胞聚集，尤其是血液中的白细胞，它们会吸收并消灭这些微生物。能够做到这一点的白细胞和其他细胞被称为‘吞噬细胞’（即吞噬细胞），确保免疫力的整个功能被称为‘吞噬作用’”。基于对传染病抵抗力基础的这些见解，梅契尼科夫与保罗·埃尔利希共同获得了1908年诺贝尔生理学或医学奖（图1）。尽管两人都因在免疫方面的发现而获奖，但两人的贡献似乎大相径庭。埃尔利希的研究并非涉及对感染的一般反应，而是关于抗体的高度特异性本质及其与产生它们的细胞的关系：“由于细胞受体显然是预先形成的，而人工产生的抗毒素只是结果，即次要的，人们很难不认为抗毒素只不过是细胞排出的成分，即过量排出的受体”。但生物系统就是这样——系统——各个部分需要协同工作。于是，一个世纪后，我们开始认识到宿主防御这两个看似不同的方面实际上是多么紧密地联系在一起。
